Nuclear mechanisms of hypoxic cerebral injury in the newborn: the role of caspases.
Our laboratory has been actively engaged in investigating mechanisms of activation of initiator caspase-9 during hypoxia in the developing newborn and fetal brains. The present review has been organized as follows: (a) the effect of hypoxia on the expression and activation of caspase-3, -8, and -9 in the newborn brain; (b) the role of nitric oxide in caspase-9, and caspase-3 activation during hypoxia in the newborn brain; (c) the role of nuclear Ca(2+)-influx in caspase-9 and caspase-3 activation during hypoxia in the newborn brain; (d) the effect of caspase-9 inhibition during hypoxia on preventing downstream events including caspase-3 activation. The results of our research investigations presented in (b), (c), and (d) elucidate mechanisms of caspase activation during hypoxia in the newborn brain. These studies provide the fundamental framework for developing neuroprotective strategies in the hypoxic newborn.
Delivoria-Papadopoulos
Maria
M
Department of Pediatrics, Drexel University College of Medicine and St Christopher's Hospital for Children, Philadelphia, PA 19102, USA. papadopoulos@DrexelMed.edu
Ashraf
Qazi M
QM
Ara
Jahan
J
Mishra
Om P
OP
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology; D053148:Caspase 3 / Q000502:physiology; D053181:Caspase 8 / Q000502:physiology; D053453:Caspase 9 / Q000502:physiology; D020169:Caspases / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D002534:Hypoxia, Brain / Q000201:enzymology*; D007231:Infant, Newborn; D023421:Models, Animal; D009569:Nitric Oxide / Q000502:physiology; D013552:Swine
D009569:Nitric Oxide; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases